Synthesis method of ezetimibe impurity

A synthesis method and technology of ezetimibe, which is applied in the field of synthesis of ezetimibe impurities, can solve the problems of reduced drug activity, increased toxic and side effects, and low drug content, and achieve low cost, high yield, and cheap raw materials Effect

Pending Publication Date: 2022-04-15
南京望知星医药科技有限公司
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Too much impurities will make the content of the drug low, and at the same time, the activity of the drug will be reduced, and the toxic and side effects will increase significantly.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Synthesis method of ezetimibe impurity
  • Synthesis method of ezetimibe impurity
  • Synthesis method of ezetimibe impurity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Dissolve 20 g of raw material compound ① in 100 ml of N,N-dimethylformamide, add 0.5 g of potassium tert-butoxide, and react at 50°C for 8 hours. The liquid phase monitors the completion of the reaction. Spin to dry, add 100 ml of water, extract with dichloromethane, dry and spin to obtain a crude product, prepare and purify to obtain 15 g of compound ② with a purity of 99% and a yield of 75%.

Embodiment 2

[0036] Dissolve 20 g of raw material compound ① in 100 ml of N,N-dimethylformamide, add 5 g of triethylamine, and react at 70°C for 48 hours. The liquid phase monitors the completion of the reaction. Spin to dry, add 100 ml of water, extract with dichloromethane, dry and spin to obtain a crude product, prepare and purify to obtain 16 g of compound ② with a purity of 99% and a yield of 80%.

Embodiment 3

[0038] Dissolve 20 g of raw material compound ① in 100 ml of N,N-dimethylformamide, add 5 g of triethylamine, and react at 60°C for 8 hours. The liquid phase monitors the completion of the reaction. Spin to dry, add 100 ml of water, extract with dichloromethane, dry and spin to obtain a crude product, prepare and purify to obtain 10 g of compound ② with a purity of 99% and a yield of 50%.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of an ezetimibe impurity, which comprises the following specific steps: step 1, dissolving a compound (1) in an organic solvent A, adding alkali, and reacting at 25-120 DEG C for 8-200 hours; step 2, dissolving the product compound (2) prepared in the step 1 in an organic solvent B, adding a desiliconizing reagent, and reacting at 25-80 DEG C for 5-48 hours to prepare a product compound (3); according to the brand-new synthesis method of the ezetimibe impurity, the used raw materials are simple, easy to obtain and available in the market; the synthesis method disclosed by the invention is reasonable in process design, simple in operation process, cheap in used raw materials, high in yield and low in cost.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, in particular to a method for synthesizing ezetimibe impurities. Background technique [0002] Ezetimibe (Ezetimibe) chemical name: 1-(4-fluorophenyl)-(3R)-[3-(4-fluorophenyl)-(3S)-hydroxypropyl]-(4S)-( 4-Hydroxyphenyl)-2-propionolactam, CAS: 163222-33-1, the specific structural formula is as follows: [0003] [0004] Ezetimibe was launched in Germany and the United States in 2002. By inhibiting the absorption of cholesterol, it can reduce the transport of intestinal cholesterol to the liver and reduce its storage; it can strengthen the removal of cholesterol in the blood, thereby reducing the level of plasma cholesterol. [0005] Ezetimibe, also known as ezetimibe and ezetimibe, is the first selective cholesterol absorption inhibitor jointly developed by Schering-Plough and Merck. This product is the first to be approved by the US FDA. Selective inhibitors of cholesterol absorpti...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & AuthorityApplications(China)
IPC IPC(8): C07D239/22
CPCC07D239/22
Inventor陈国雨石庆然朱祖强
Owner南京望知星医药科技有限公司